Monday, July 31, 2023

PLGA-PEG-PLGA Thermogel From PolySciTech:Akina used in development of gemcitabine and rapamycin delivery system for pancreatic cancer therapy.

 

In 2021, pancreatic cancer was the 12th most common malignant tumor worldwide with a high mortality rate and poor prognosis. Researchers at Chungbuk National University, Huons Co., Sookmyung Women's University (Korea) used PLGA-PEG-PLGA (AK012 and AK019) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create thermogel solutions for delivery of synergistic gemcitabine and rapamycin drugs as a treatment for pancreatic cancer. This research holds promise to provide therapy against this deadly disease. Read more: Kim, Seo Yeon, Min Jeong Jo, Moon Sup Yoon, Chae Eun Jin, Yu Been Shin, Jae Min Lee, Hee Ji Shin et al. "Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy." Journal of Controlled Release 360 (2023): 796-809. https://www.sciencedirect.com/science/article/pii/S0168365923004340

“Highlights: Gemcitabine and rapamycin show a synergistic effect at a molar ratio of 11:1. The 25% w/v mixed PLGA-PEG-PLGA thermogel (g(GR)) becomes a gel at 32 °C. The g(GR) has high encapsulation efficiency (>75%) and small size (<100 nm). The g(GR) most effectively suppressed Panc-1-luc2 tumor spheroid. The g(GR) showed no toxicity and suppressed tumors most effectively in mice. Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer–related death and has a poor 5–year overall survival. The superior therapeutic benefits of combination or co–administration of drugs as intraperitoneal chemotherapy have increased interest in developing strategies to deliver chemotherapeutic agents to patients safely. In this study, we prepared a gel comprising the thermosensitive poly(lactide–co–glycolide)–b–poly(ethylene glycol)–b–poly(lactide–co–glycolide) (PLGA–PEG–PLGA) polymer and gemcitabine (GEM), which is currently used as the primary chemotherapy for PDAC and rapamycin (RAPA), a mammalian TOR (mTOR) inhibitor, to deliver the drug through intraperitoneal injection. We performed in vitro cytotoxicity experiments to verify the synergistic effects of the two drugs at different molar ratios and characterized the physicochemical properties of the GEM, RAPA, and GEM/RAPA–loaded thermosensitive PLGA–PEG–PLGA gels, hereafter referred to as (g(G), g(R), and g(GR)), respectively. The g(GR) comprising PLGA–PEG–PLGA polymer (25% w/v) and GEM and RAPA at a molar ratio of 11:1 showed synergism and was optimized. An in vitro cytotoxicity assay was performed by treating Panc–1–luc2 tumor spheroids with g(G), g(R), or g(GR). The g(GR) treatment group showed a 2.75–fold higher inhibition rate than the non–treated (NT) and vehicle–treated groups. Furthermore, in vivo drug release assay in mice by intraperitoneal injection of g(G), g(R), or g(GR) showed a more rapid release rate of GEM than RAPA, similar to the in vitro release pattern. The drugs in the gel were released faster in vivo than in vitro and degraded in 48 h. In addition, g(GR) showed the highest anti–tumor efficacy with no toxicity to mice. These results provide evidence for the safety and efficacy of g(GR) for intraperitoneal drug delivery. This study will assist in developing and clinically administering topical anti–cancer formulations. Keywords: Combination therapy Pancreatic cancer therapy Intraperitoneal injection Gemcitabine Rapamycin Thermosensitive hydrogel”

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